Design, Structure-Activity Relationships, and Computational Modeling Studies of a Series of α-Helix Biased, Ultra-Short Glucagon-like Peptide-1 Receptor Agonists.

A systematic structure-activity and computational modeling analysis of a series of glucagon-like peptide-1 receptor (GLP-1R) agonists based upon an ultra-short GLP-1 peptide, H-His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Bip-Bip-NH2, was conducted. This highly potent 11-mer peptide led to a deeper understanding of the α-helical bias of strategic α-methylation within the linear parent template as well as optimization of GLP-1R agonist potency by 1000-fold. These data were correlated with previously reported co-structures of both full-length GLP-1 analogs and progenitor N-terminal GLP-1 fragment analogs related to such ultra-short GLP-1R agonist peptides.

Exploring Condition-Specific Variability in the Ureteral Stent Microbiome.

(1) Background: Indwelling ureteral stents are commonly used urological devices to maintain ureteral patency, yet they have been associated with complications such as infections. Some studies have shown that bacteria adhere to and create an antimicrobial-resistant biofilm on stents. One factor that may impact biofilm formation is the original condition informing stent placement, such as kidney stones and renal allografts.

The Occurrence of Senescence in the Arteriovenous Fistula in the Rat.

Background: Maturational failure of dialysis arteriovenous fistulas (AVFs) not uncommonly occurs and is of considerable and timely importance. Our prior studies demonstrate that senescence, a phenotypic process that promotes vascular and other diseases, occurs in the murine AVF. In the present study, we examined whether senescence also occurs in the rat AVF model and the effect of compounds that inhibit or accelerate senescence.

Manipulating the Gut Microbiome in Urinary Tract Infection-Prone Patients.

Although antibiotics remain the mainstay of urinary tract infection treatment, many affected women can be caught in a vicious cycle in which antibiotics given to eradicate one infection predispose them to develop another. This effect is primarily mediated by disturbances in the gut microbiome that both directly enrich for uropathogenic overgrowth and induce systemic alterations in inflammation, tissue permeability, and metabolism that also decrease host resistance to infection recurrences. Here, we discuss nonantibiotic approaches to manipulating the gut microbiome to reverse the systemic consequences of antibiotics, including cranberry supplementation and other dietary approaches, probiotic administration, and fecal microbiota transplantation.